Surgical tools and techniques for stimulation

ABSTRACT

Apparatus for treating a subject is provided, the apparatus comprising (a) a stimulation device ( 352 ), adapted to be implanted in a vicinity of a site selected from the list consisting of: a sphenopalatine ganglion (SPG) ( 52 ) of the subject and a neural tract originating in or leading to the SPG; and (b) a connecting element ( 356 ), coupled to the stimulation device ( 352 ), and adapted to be passed through at least a portion of a greater palatine canal ( 282 ) of the subject. Also provided is a method for implanting a treatment stimulation device ( 352 ) in a vicinity of a site of a subject, the method comprising passing the device ( 352 ) through a greater palatine foramen ( 22 ) of the subject, and bringing the device ( 352 ) into contact with the vicinity of the site, the site selected from the list consisting of: a sphenopalatine ganglion (SPG) ( 52 ) of the subject and a neural tract originating in or leading to the SPG.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority from U.S. Provisional PatentApplication 60/426,180, filed Nov. 14, 2002, entitled; “Surgical toolsand techniques for stimulation,” which is assigned to the assignee ofthe present application and is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to medical procedures andelectronic devices. More specifically, the invention relates to the useof electrical devices for implantation in the head and surgicaltechniques for implanting the devices.

BACKGROUND OF THE INVENTION

The blood-brain barrier (BBB) is a unique feature of the central nervoussystem (CNS), which isolates the brain from the systemic bloodcirculation. To maintain the homeostasis of the CNS, the BBB preventsaccess to the brain for many substances circulating in the blood.

The BBB is formed by a complex cellular system of endothelial cells,astroglia, pericytes, perivascular macrophages, and a basal lamnina.Compared to other tissues, brain endothelia have the most intimatecell-to-cell connections: endothelial cells adhere strongly to eachother, forming structures specific to the CNS called “tight junctions”or zonula occludens. They involve two opposing plasma membranes, whichform a membrane fusion with cytoplasmic densities on either side. Thesetight junctions prevent cell migration or cell movement betweenendothelial cells. A continuous uniform basement membrane surrounds thebrain capillaries. This basal lamina encloses contractile cells calledpericytes, which form an intermittent layer and probably play some rolein phagocytosis activity and defense if the BBB is breached. Astrocyticend feet, which cover the brain capillaries, build a continuous sleeveand maintain the integrity of the BBB by the synthesis and secretion ofsoluble growth factors (e.g., gamma-glutamyl transpeptidase) essentialfor the endothelial cells to develop their BBB characteristics.

Because of the BBB, certain non-surgical treatments of the brain basedupon systemic introduction of compounds through the bloodstream havebeen ineffective or less effective. For example, chemotherapy has beenrelatively ineffective in the treatment of CNS metastases of systemiccancers (e.g., breast cancer, small cell lung cancer, lymphoma, and germcell tumors) despite clinical regression and even complete remission ofthese tumors in non-CNS systemic locations. The most important factorsdetermining drug delivery from blood into the CNS are lipid solubility,molecular mass, and electrical charge. A good correlation exists betweenthe lipid solubility of a drug, expressed as the octanol/water partitioncoefficient, and the drug's ability to penetrate or diffuse across theBBB. This is particularly relevant for drugs with molecular weightssmaller than 600 Dalton (Da). The normal BBB prevents the passage ofionized water soluble drugs with molecular weight greater than 180 Da.Most currently available effective chemotherapeutic agents, however,have a molecular weight between 200 and 1200 Da Therefore, based both ontheir lipid solubilities and molecular masses, the passage of manyagents is impeded by the BBB.

In addition to transcellular diffusion of lipophilic agents, there areseveral specific transport mechanisms to carry certain molecules acrossthe brain's endothelial cells. Specific transport proteins exist forrequired molecules, such as glucose and amino acids. Additionally,absorptive endocytosis and transcytosis occur for cationized plasmaproteins. Specific receptors for certain proteins, such as transferrinand insulin, mediate endocytosis and transport across the cell.

Non-surgical treatment of neurological disorders is generally limited tosystemic introduction of compounds such as neuropharmaceuticals andother neurologically active agents that might remedy or modifyneurologically related activities and disorders. Such treatment islimited, however, by the relatively small number of known compounds thatpass through the BBB. Even those that do cross the BBB often produceadverse reactions in other parts of the body or in non-targeted regionsof the brain

There have been a number of different studies regarding efforts to crossthe BBB, specifically with regard to overcoming the limited access ofdrugs to the brain. Such efforts have included, for example, chemicalmodification, development of more hydrophobic analogs, or linking anactive compound to a specific carrier. Transient opening of the BBB inhumans has been achieved by intracarotid infusion of hypertonic mannitolsolutions or bradykinin analogs. Also, modulation of the P-glycoprotein,whose substrates are actively pumped out of brain cells into capillarylumens, has been found to facilitate the delivery of drugs to the brain.

The sphenopalatine ganglion (SPG) is a neuronal center located in thebrain behind the nose. It consists of parasympathetic neuronsinnervating the middle cerebral and anterior cerebral lumens, the facialskin blood vessels, and the lacrimal glands. Activation of this ganglionis believed to cause vasodilation of these vessels. A second effect ofsuch stimulation is the opening of pores in the vessel walls, causingplasma protein extravasation (PPE). This effect allows better transportof molecules from within these blood vessels to surrounding tissue.

The middle and anterior cerebral arteries provide the majority of theblood supply to the cerebral hemispheres, including the frontal andparietal lobes in their entirety, the insula and the limbic system, andsignificant portions of the following structures: the temporal lobes,internal capsule, basal ganglia and thalamus. These structures areinvolved in many of the neurological and psychiatric diseases of thebrain. Currently the SPG is a target of manipulation in clinicalmedicine, mostly in attempted treatments of severe headaches, such ascluster headaches. The ganglion is blocked either on a short-term basis,by applying lidocaine, or permanently, by ablation with a radiofrequency probe. In both cases the approach is through the nostrils.

The following references, which are incorporated herein by reference,may be useful:

Delepine, L., Aubineau, P., “Plasma protein extravasation induced in therat dura mater by stimulation of the parasympathetic sphenopalatineganglion,” Experimental Neurology, 147,389-400 (1997).

Hara, H., Zhang, Q. J., Kuroyanagi, T., Kobayashi, S., “Parasympatheticcerebrovascular innervation: An anterograde tracing from thesphenopalatine ganglion in the rat,” Neurosurgery, 32, 822-827 (1993).

Jolliet-Raint, P., Tillement, J. P., “Drug transfer across theblood-brain barrier and improvement of brain delivery,” Fundam. Clin.Pharmacol., 13, 16-25 (1999).

Kroll, R. A., Neuwelt, E. A., “Outwitting the blood brain barrier fortherapeutic purposes: Osmotic opening and other means,” Neurosurgery,42, 1083-1100(1998).

Sanders, M., Zuurmond, W. W., “Efficacy of sphenopalatine ganglionblockade in 66 patients suffering from cluster headache: A 12-70 monthfollow-up evaluation,” Journal of Neurosurgery, 87, 876-880 (1997).

Seylaz, J., Hara, H., Pinard, E., Mraovitch, S., MacKenzie, E. T.,Edvinsson, L, “Effects of stimulation of the sphenopalatine ganglion oncortical blood flow in the rat,” Journal of Cerebral Blood Flow andMetabolism, 8, 875-878 (1988).

Van de Waterbeemd, H., Camenisch, G., Folkers, G., Chretien, J. R,Raevsky, O. A., “Estimation of blood brain barrier crossing of drugsusing molecular size and shape and h bonding descriptors,” Journal ofDrug Targeting, 6, 151-165 (1998).

Suzuki, N., Hardebo, J. E., Kahrstrom, J., Owman, C., “Selectiveelectrical stimulation of postganglionic cerebrovascular parasympatheticnerve fibers originating from the sphenopalatine ganglion enhancescortical blood flow in the rat,” Journal of Cerebral Blood Flow andMetabolism, 10, 383-391 (1990).

Suzuki, N., Hardebo, J. E., Kahrstrom, J., Owrnan, C. H., “Effect oncortical blood flow of electrical stimulation of trigeminalcerebrovascular nerve fibres in the rat,” Acta Physiol. Scand., 138,307-315 (1990).

Branston N M, “The physiology of the cerebrovascular parasympatheticinnervation,” British Journal of Neurosurgery 9:319-329 (1995).

Branston N M et al., “Contribution of cerebrovascular parasympatheticand sensory innervation to the short-term control of blood flow in ratcerebral cortex,” J Cereb Blood Flow Metab 15(3):525-31 (1995).

Toda N et al., “Cerebral vasodilation induced by stimulation of thepterygopalatine ganglion and greater petrosal nerve in anesthetizedmonkeys,” Neuroscience 96(2):393-398 (2000).

Seylaz J et al., “Effect of stimulation of the sphenopalatine ganglionon cortical blood flow in the rat,” J Cereb Blood Flow Metab 8(6):875-8(1988).

PCT Patent Publication WO 01/85094 to Shalev and Gross, which isassigned to the assignee of the present patent application and whosedisclosure is incorporated herein by reference, describes methods andapparatus for stimulating the sphenopalatine ganglion to modifyproperties of the blood brain barrier and cerebral blood flow for thetreatment of medical conditions. Treatment is accomplished directly viastimulation of the sphenopalatine ganglion and/or indirectly by thefacilitation of drug transport across the blood brain barrier viastimulation of the sphenopalatine ganglion.

U.S. Pat. No. 6,526,318 to Ansarinia and related PCT Patent PublicationWO 01/97905 to Ansarinia, whose disclosure is incorporated herein byreference, describes a method for treating a patient by placing at leastone electrode on or proximate to at least one of the patient'ssphenopalatine ganglia, sphenopalatine nerves, or vidian nerves, andactivating the electrode to apply an electrical signal and/or a medicalsolution to at least one of those ganglia or nerves. The '318 patent and'905 publication also describe surgical techniques for implanting theelectrode via a coronoid notch of the patient

U.S. Pat. No. 6,405,079 to Ansarinia, whose disclosure is incorporatedherein by reference, describes methods for treating medical conditionsby implanting one or more electrodes in regions of the sinus andapplying electrical stimulation and/or medical solutions to theimplantation site. The '079 patent also describes surgical techniquesfor implanting the electrode.

SUMMARY OF THE INVENTION

In some embodiments of the present invention, apparatus for stimulatingthe “sphenopalatine ganglion (SPG) system,” as defined hereinbelow, issurgically implanted so as to stimulate the SPG system. Typically, thesurgical procedure is performed in a relatively minimally-invasivemanner to reduce patient discomfort during and after the procedure. Onceimplanted, the apparatus typically delivers the energy to the SPG systemin order to control and/or modify SPG-related behavior, e.g., in orderto induce changes in cerebral blood flow and/or to modulate permeabilityof the blood-brain-barrier (BBB). These embodiments may be used in manymedical applications, such as, by way of illustration and notlimitation, (a) the treatment of cerebrovascular disorders such asstroke, (b) the treatment of migraine headaches, (c) the treatment ofAlzheimer's disease, (d) the facilitation of drug transport across theBBB, and/or (e) the facilitation of extraction of analytes from thebrain.

In the present patent application, including the claims, “SPG system”means the SPG and associated neuroanatomical structures, includingneural tracts originating in or reaching the SPG, including outgoing andincoming parasympathetic and sympathetic tracts, which tracts includepreganglionic fibers of the SPG (fibers contained within the vidiannerve) and postganglionic fibers of the SPG (fibers that travelanterogradely from the SPG toward the brain vascular bed, including theanterior and posterior ethmoidal nerves, and including the retro-orbitalbranches of the SPG, which are fibers that connect the SPG with orbitalneural structures).

It is to be appreciated that, in general, the techniques describedherein may be applied directly, or applied with changes mutatismutandis, so as to facilitate stimulation of one or more of thefollowing and thereby facilitate treatment of a medical condition:

-   -   a sphenopalatine ganglion (SPG) (also called a pterygopalatine        ganglion);    -   an anterior ethmoidal nerve;    -   a posterior ethmoidal nerve;    -   a communicating branch between the anterior ethmoidal nerve and        the SPG (retro-orbital branch);    -   a communicating branch between the posterior ethmoidal nerve and        the SPG (retro-orbital branch)    -   a nerve of the pterygoid canal (also called a vidian nerve),        such as a greater superficial petrosal nerve (a preganglionic        parasympathetic nerve) or a lesser deep petrosal nerve (a        postganglionic sympathetic nerve);    -   a greater palatine nerve;    -   a lesser palatine nerve;    -   a sphenopalatine nerve;    -   a communicating branch between the maxillary nerve and the        sphenopalatine ganglion;    -   a nasopalatine nerve;    -   a posterior nasal nerve;    -   an infraorbital nerve;    -   an otic ganglion;    -   an afferent fiber going into the otic ganglion; and/or    -   an efferent fiber going out of the otic ganglion.

According to some embodiments of the present invention, a method andapparatus are provided to facilitate placement of at least one electrodeadjacent to the SPG via an endoscopic transpalatine approach to the SPG.Typically, local anesthetic is applied to the oral palatine mucosa and agreater palatine block is performed prior to a mucoperiosteal incisionproximate the greater palatine foramen to reveal the contents of theforamen. A trocar comprising a flexible guide tube is typically insertedvertically through the incision to provide access for endoscopicdissection and visualization tools, which are used for the subsequentportion of the procedure. Typically, the endoscopic tools are used forsubperiosteal dissection to detach the greater palatine canal contentsfrom the osseous part of the canal and provide access to the vidianforamen and a portion of the SPG.

Typically, at least one electrode is placed next to or in contact withthe SPG via the flexible guide tube. In an embodiment, each electrode isflat so as to provide a large contact area between the electrode andSPG. Typically, the electrode is flexible enough to be rolled up andinserted through the trocar and guide tube and sufficiently elastic toresume a generally planar shape once through the trocar and guide tube.Additionally or alternatively, the electrode has a curved shape suchthat it may be hooked around a nerve in the SPG system, such as thevidian nerve.

Typically, the at least one electrode comprises two or more electrodes,driven to operate in a multi-polar mode (e.g., in a bipolar mode for thecase of two electrodes).

According to some embodiments of the present invention, a method andapparatus are provided to facilitate placement of at least one electrodeadjacent to the SPG via a transpalatine approach to the SPG. The area ofthe greater palatine foramen is anesthetized, and a full-thicknessmucogingival incision is performed at the midline of the hard palate,including about 0.5 cm of the soft palate. Two releasing incisions areperformed at the ends of the midline incision. A mucoperiosteal flap israised, and the greater palatine neurovascular bundle is carefullyexposed, revealing the contents of the greater palatine foramen. Astylet is inserted posteriorly through the greater palatine canal to thegreater palatine neurovascular bundle, and supported against theposterior wall of the greater palatine canal. The stylet is removed, anda series of passive tip periosteal elevators, having successivelygreater distal shaft diameters, is used to widen the path created usingthe stylet.

An introducer is provided for introducing a neural stimulator into thegreater palatine canal. The introducer typically comprises a handle formanipulating the introducer, a rod, and a protective sleeve. The neuralstimulator typically comprises an electrode support, a receiver, and aconnecting tube. The electrode support is mounted on the introducer byfitting the protective sleeve of the introducer over the electrodesupport. During the surgical procedure, after the greater palatine canalhas been widened, the introducer is inserted into the greater palatinecanal, and a surface of the stimulator that comprises at least oneelectrode is placed in contact with the posterior aspect of thesphenopalatine ganglion.

Subsequent to placement of the at least one electrode, proper placementis typically assured by running a test current through the at least oneelectrode and monitoring the physiological effect on the patient.Typically, once proper placement of the at least one electrode isassured, the at least one electrode is coupled to a control unit. Forsome applications, the control unit is implanted in the patient.Alternatively, an external control unit is used to control the at leastone electrode.

According to some embodiments of the present invention, a method andapparatus are provided to facilitate placement of at least one electrodeadjacent to the SPG via a combined trans-maxillary sinus and trans-nasalendoscopic assisted approach. Typically, after administration ofappropriate anesthesia, the posterior wall of the maxillary sinus iscarefully dissected and the anterior part of the sphenopalatine fossa isdissected via a trans-maxillary approach. The dissection is typicallyperformed approximately 0.5 mm from the medial wall of the maxillarysinus, under direct endoscopic visualization. Subsequently, a completenasal endoscopic examination is typically performed on both sides, andthen, under direct visualization, an incision is made about 0.4 mm—about0.8 mm under the second conchae on the operating side. Typically, amucoperiosteal flap is raised posteriorly and inferiorly, to allow thesphenopalatine artery to be dissected and clamped. The sphenopalatinefossa is then typically approached under direct endoscopicvisualization, and the lateral wall of the nose is penetrated.Subsequently, in an embodiment, the SPG is approached via the maxillarysinus. In another embodiment, the SPG is accessed via a trans-nasalapproach.

Typically, an introducer, comprising a hollow tube, is inserted throughthe dissected tissue to provide a pathway for introduction of the atleast one electrode, which comprises a lead wire, to a region adjacentto the SPG. In an embodiment the electrodes are flat, such that a largesurface area is available for contact with the SPG. In anotherembodiment, one or more of the electrodes are curved, so as to wraparound a portion of a nerve such as the vidian nerve, or another nervein the SPG system.

Once the at least one electrode is placed, a controlled stimulation istypically performed by passing a current through the lead wire to theelectrode to confirm that the electrode is properly placed. Evaluationof the proper placement of the at least one electrode comprises one ormore of: (1) evaluating the vasodilatation of blood vessels in the eye,(2) assessment of cerebral blood flow by using a transcranial Doppler,(3) assessment of forehead perfusion by using Laser Doppler, and (4)assessment of forehead perfusion by a temperature sensor. In anembodiment, once proper placement of the electrodes has been verified,the electrodes are coupled to an implantable control unit. In anotherembodiment, the electrodes are coupled to an external control unit bywired or wireless means.

There is therefore provided, in accordance with an embodiment of thepresent invention, apparatus for treating a subject, including:

a stimulation device, adapted to be implanted in a vicinity of a siteselected from the list consisting of: a sphenopalatine ganglion (SPG) ofthe subject and a neural tract originating in or leading to the SPG; and

a connecting element, coupled to the stimulation device, and adapted tobe passed through at least a portion of a greater palatine canal of thesubject.

In an embodiment, the portion of the greater palatine canal has a lengthof at least about 2 cm, and the connecting element is adapted to bepassed through the portion.

In an embodiment, the connecting element includes at least one mark,adapted to indicate a depth of insertion of the stimulation device inthe greater palatine canal.

In an embodiment, the stimulation device is adapted to stimulate thesite, and to configure the stimulation to be sufficient to induce achange in cerebral blood flow of the subject

In an embodiment, the stimulation device is adapted to stimulate thesite, and to configure the stimulation to be sufficient to modulatepermeability of a blood-brain-barrier of the subject.

In an embodiment, the site includes the SPG of the subject, and thestimulation device is adapted to be implanted in the vicinity of theSPG.

In an embodiment, the site includes a vidian nerve of the subject, andthe stimulation device is adapted to be implanted in the vicinity of thevidian nerve.

In an embodiment, the site includes an ethmoidal nerve of the subject,and the stimulation device is adapted to be implanted in the vicinity ofthe ethmoidal nerve.

In an embodiment, the site includes a retro-orbital branch of the SPG ofthe subject, and the stimulation device is adapted to be implanted inthe vicinity of the retro-orbital branch.

In an embodiment, the apparatus includes an introducer, adapted formounting the stimulation device thereon, and to be passed through the atleast a portion of the greater palatine canal.

In an embodiment, the stimulation device includes at least oneelectrode. For example, the electrode may be configured to wrap around anerve of the subject in the vicinity of the site.

In an embodiment, the apparatus includes a stimulator, coupled to theconnecting element, and adapted to be fixed to a hard palate of thesubject. For example, the stimulator may be adapted to be coupled to thehard palate in a supraperiosteal region thereof. For some applications,the stimulator is adapted to be coupled to an upper surface of the hardpalate in a nasal cavity of the subject. For some applications, thestimulator is adapted to be coupled to a lower surface of the hardpalate.

There is further provided, in accordance with an embodiment of thepresent invention, apparatus for insertion into a greater palatine canalof a subject, including a stylet, which includes:

a proximal rod shaft, having a first diameter; and

a distal rod shaft, having a second diameter less than the firstdiameter, such that a region between the proximal rod shaft and thedistal rod shaft is shaped so as to define a shoulder which is adaptedto prevent insertion of the distal rod shaft into a sphenopalatine fossaof the subject beyond a depth of the greater palatine canal.

In an embodiment, the distal rod shaft includes a cutting implement,located in a vicinity of a distal tip of the shaft.

In an embodiment, the proximal rod shaft has a length of between about20 mm and about 150 mm.

In an embodiment, the first diameter is between about 1.5 mm and about 6mm.

In an embodiment, the distal rod shaft has a length of between about 3mm and about 20 mm.

In an embodiment, the second diameter is between about 1 mm and about1.5 mm.

In an embodiment, the apparatus includes a periosteal elevator forinsertion into the greater palatine canal, the elevator including atleast one mark adapted to indicate a depth of insertion of theperiosteal elevator in the greater palatine canal.

There is still further provided, in accordance with an embodiment of thepresent invention, apparatus for insertion into a greater palatine canalof a subject, including a periosteal elevator, which includes at leastone mark adapted to indicate a depth of insertion of the periostealelevator in the greater palatine canal.

There is also provided, in accordance with an embodiment of the presentinvention, a method for implanting a treatment stimulation device in avicinity of a site of a subject, including:

passing the device through a greater palatine foramen of the subject;and

bringing the device into contact with the vicinity of the site, the siteselected from the list consisting of: a sphenopalatine ganglion (SPG) ofthe subject and a neural tract originating in or leading to the SPG.

There is also provided, in accordance with an embodiment of the presentinvention, a method for implanting a treatment stimulation device in avicinity of a site of a subject, including:

passing the device through at least a portion of a greater palatinecanal of the subject; and

bringing the device into contact with the vicinity of the site, the siteselected from the list consisting of: a sphenopalatine ganglion (SPG) ofthe subject and a neural tract originating in or leading to the SPG.

For some applications, the site includes the SPG of the subject, andbringing the device into contact with the vicinity of the site includesbringing the device into contact with the vicinity of the SPG.

For some applications, the site includes a vidian nerve of the subject,and bringing the device into contact with the vicinity of the siteincludes bringing the device into contact with the vicinity of thevidian nerve.

For some applications, the site includes an ethmoidal nerve of thesubject, and bringing the device into contact with the vicinity of thesite includes bringing the device into contact with the vicinity of theethmoidal nerve.

For some applications, the site includes a retro-orbital branch of theSPG of the subject, and bringing the device into contact with thevicinity of the site includes bringing the device into contact with theretro-orbital branch.

For some applications, bringing the device into contact includes:

applying stimulation with the device;

observing one or more physiological responses of the subject to thestimulation; and

verifying desired placement of the device responsive to the observation.

For some applications, bringing the device into contact includesapplying stimulation with the device, and configuring the stimulation tobe sufficient to induce a change in cerebral blood flow of the subject.For some applications, bringing the device into contact includesapplying stimulation with the device, and configuring the stimulation tobe sufficient to modulate permeability of a blood-brain-barrier of thesubject.

For some applications, the stimulation device includes at least oneelectrode, and bringing the device into contact includes bringing theelectrode into contact with the vicinity of the site. For someapplications, bringing the electrode into contact includes wrapping theelectrode around a nerve of the subject in the vicinity of the site.

For some applications, the stimulation device includes a stimulator, themethod including fixing the stimulator to a hard palate of the subjectFor example, fixing the stimulator to the hard palate may includecoupling the stimulator to a supraperiosteal region of the hard palate.In an embodiment, fixing the stimulator to the hard palate includescoupling the stimulator to an upper surface of the hard palate in anasal cavity of the subject. In an embodiment, fixing the stimulator tothe hard palate includes coupling the stimulator to a lower surface ofthe hard palate.

In an embodiment, passing the device through the greater palatineforamen includes determining a depth of insertion of the device in agreater palatine canal of the subject by observing at least one mark onthe device indicative of the depth of the insertion.

In an embodiment, passing the device through the greater palatineforamen includes widening a greater palatine canal of the subject usinga series of periosteal elevators having successively greater diameters.

In an embodiment, passing the device through the greater palatineforamen includes widening a greater palatine canal of the subject usinga series of tools having successively greater diameters.

In an embodiment, passing the device through the greater palatineforamen includes mounting the device on an introducer, and passing theintroducer through the greater palatine foramen.

In an embodiment, passing the device through the portion of the greaterpalatine canal includes determining a depth of insertion of the devicein the greater palatine canal by observing at least one mark on thedevice indicative of the depth of the insertion.

In an embodiment, passing the device through the at least a portion ofthe greater palatine canal includes passing the device through at leastabout 2 cm of the greater palatine canal.

In an embodiment, passing the device through the at least a portion ofthe greater palatine canal includes widening the portion using a seriesof periosteal elevators having successively greater diameters.

In an embodiment, passing the device through the at least a portion ofthe greater palatine canal includes widening the portion using a seriesof tools having successively greater diameters.

In an embodiment, passing the device through the at least a portion ofthe greater palatine canal includes mounting the device on anintroducer, and passing the introducer through the portion.

There is yet additionally provided, in accordance with an embodiment ofthe present invention, a method for implanting a treatment device in avicinity of a site of a subject, including:

passing the device through a trans-maxillary sinus of the subject; and

bringing the device into contact with the vicinity of the site, the siteselected from the list consisting of: a sphenopalatine ganglion (SPG) ofthe subject and a neural tract originating in or leading to the SPG.

In an embodiment, the site includes the SPG of the subject, and bringingthe device into contact with the vicinity of the site includes bringingthe device into contact with the vicinity of the SPG.

In an embodiment, the site includes a vidian nerve of the subject, andbringing the device into contact with the vicinity of the site includesbringing the device into contact with the vicinity of the vidian nerve.

In an embodiment, the site includes an ethmoidal nerve of the subject,and bringing the device into contact with the vicinity of the siteincludes bringing the device into contact with the vicinity of theethmoidal nerve.

In an embodiment, the site includes a retro-orbital branch of the SPG ofthe subject, and bringing the device into contact with the vicinity ofthe site includes bringing the device into contact with theretro-orbital branch.

In an embodiment, bringing the device into contact includes:

applying stimulation with the device;

observing one or more physiological responses of the subject to thestimulation; and

verifying desired placement of the device responsive to the observation.

There is still additionally provided, in accordance with an embodimentof the present invention, a method for implanting a treatment device ina vicinity of a site of a subject, including:

passing the device through a sphenopalatine foramen canal of thesubject; and

bringing the device into contact with the vicinity of the site, the siteselected from the list consisting of a sphenopalatine ganglion (SPG) ofthe subject and a neural tract originating in or leading to the SPG.

In an embodiment, the site includes the SPG of the subject, and bringingthe device into contact with the vicinity of the site includes bringingthe device into contact with the vicinity of the SPG.

In an embodiment, the site includes a vidian nerve of the subject, andbringing the device into contact with the vicinity of the site includesbringing the device into contact with the vicinity of the vidian nerve.

In an embodiment, the site includes an ethmoidal nerve of the subject,and bringing the device into contact with the vicinity of the siteincludes bringing the device into contact with the vicinity of theethmoidal nerve.

In an embodiment, the site includes a retro-orbital branch of the SPG ofthe subject, and bringing the device into contact with the vicinity ofthe site includes bringing the device into contact with theretro-orbital branch.

In an embodiment, bringing the device into contact includes:

applying stimulation with the device;

observing one or more physiological responses of the subject to thestimulation; and

verifying desired placement of the device responsive to the observation.

There is also provided, in accordance with an embodiment of the presentinvention, a method for implanting a treatment device in a vicinity ofan ethmoidal nerve of a subject, including:

passing the device through an ethmoidal foramen of the subject; and

bringing the device into contact with the vicinity of the ethmoidalnerve.

In an embodiment, the ethmoidal nerve includes an anterior ethmoidalnerve of the subject, and bringing the device into contact includesbringing the device into contract with the vicinity of the anteriorethmoidal nerve.

In an embodiment, the ethmoidal nerve includes a posterior ethmoidalnerve of the subject, and bringing the device into contact includesbringing the device into contract with the vicinity of the posteriorethmoidal nerve.

In an embodiment, bringing the device into contact includes:

applying stimulation with the device;

observing one or more physiological responses of the subject to thestimulation; and

verifying desired placement of the device responsive to the observation.

The present invention will be more fully understood from the followingdetailed description of the embodiments thereof, taken together with thedrawings in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a pictorial illustration of the roof of the oral cavity,showing a site for an incision, in accordance with an embodiment of thepresent invention;

FIG. 2 is a schematic illustration of endoscopic apparatus for accessingthe sphenopalatine ganglion (SPG) system, in accordance with anembodiment of the present invention;

FIG. 3 is a pictorial illustration of an endoscopic tool accessing theSPG system, in accordance with an embodiment of the present invention;

FIGS. 4A and 4B are schematic illustrations of an electrode introducerfor placing an electrode in the SPG system, in accordance with anembodiment of the present invention;

FIGS. 5A, 5B, and 5C are schematic illustrations of electrode supportsto be placed in the SPG system, in accordance with embodiments of thepresent invention;

FIG. 6 is a schematic illustration of an electrode to be hooked around anerve in the SPG system, in accordance with an embodiment of the presentinvention;

FIG. 7 is a schematic illustration of an endoscopic tool for placing anelectrode in the SPG system, in accordance with an embodiment of thepresent invention;

FIG. 8 is a schematic illustration of a system for supporting electricalleads during placement of an electrode in the SPG system, in accordancewith an embodiment of the present invention;

FIGS. 9A and 9B are schematic, partially sectional illustrations ofreceivers for receiving control and power signals to drive an electrodethat is placed in the SPG system, in accordance with embodiments of thepresent invention;

FIG. 10 is a schematic, sectional illustration of the placement of anelectrode in the SPG system and a control unit on the upper jaw, inaccordance with an embodiment of the present invention;

FIG. 11 is a schematic, pictorial illustration of the placement of anelectrode adjacent to the anterior ethmoidal nerve and a control unit onthe orbital rim, in accordance with an embodiment of the presentinvention;

FIG. 12 is a schematic, pictorial illustration showing incisions in aroof of an oral cavity and associated anatomical structures, inaccordance with an embodiment of the present invention;

FIG. 13 is a schematic illustration of a stylet, in accordance with anembodiment of the present invention;

FIG. 14 is a schematic, pictorial illustration of a posterolateral roofof an oral cavity, in accordance with an embodiment of the presentinvention;

FIGS. 15A and 15B are schematic illustrations of a passive tipperiosteal elevator used to widen the path created using the stylet ofFIG. 13, in accordance with embodiments of the present invention;

FIG. 16 is a schematic illustration of an implantable neural stimulator,in accordance with an embodiment of the present invention;

FIG. 17 shows an electrode configuration for use with an electrodesupport of the stimulator of FIG. 16, in accordance with an embodimentof the present invention;

FIG. 18 is a schematic illustration of an electrode introducer, inaccordance with an embodiment of the present invention;

FIG. 19 is a schematic illustration of the stimulator of FIG. 16 mountedon the electrode introducer of FIG. 18, in accordance with an embodimentof the present invention; and

FIG. 20 is a schematic, sectional illustration of the placement of anelectrode in the SPG system and a control unit on the upper jaw, inaccordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS

FIG. 1 is a schematic, pictorial illustration showing a roof of an oralcavity 20 and associated anatomical structures, where dissectioncommences in a surgical procedure to access the sphenopalatine ganglion(SPG) system, in accordance with an embodiment of the present invention.In this embodiment, soft tissue is dissected to expose a greaterpalatine foramen 22, in order to allow access via the greater palatinecanal (also known as the pterygopalatine canal) to the SPG system bymeans of an endoscopic transpalatine approach.

To start the procedure, the patient is typically positioned with an openmouth, and a topical and local anesthetic is applied to the oralpalatine mucosa Typically, after the local anesthetic has taken thedesired effect (typically after about 2-3 minutes), a greater palatinenerve block is performed. Greater palatine foramen 22 is then located,typically by the anatomical landmark of a second upper molar 24.Typically, a mucoperiosteal incision is made in front of the location ofgreater palatine foramen 22, and the contents of the foramen aredissected and revealed.

FIG. 2 is a schematic illustration showing endoscopic apparatus 30,which is used in the surgical procedure to access the SPG once thecontents of greater palatine foramen 22 have been dissected andrevealed, in accordance with an embodiment of the present invention.Apparatus 30 comprises a handle 38, which contains a keyhole opening 42,through which a flexible hollow sleeve 36 is placed. Typically sleeve 36serves as a conduit and guide for introduction of endoscopic tools,while handle 38 is used to move and orient sleeve 36 and any introducedendoscopic tools. Further typically, sleeve 36 comprises a slit 43,running the length of the sleeve, which is lined up with keyhole opening42, such that handle 38 and sleeve 36 can be removed from around wiressubsequently introduced through the sleeve.

In some embodiments of the present invention, hollow sleeve 36 isadapted to permit a flexible shaft 34 to be introduced and advanced to adesired operative site. Flexible shaft 34 is typically adapted such thata surgical tool 40 may be attached to the distal end of the shaft. Forexample, FIG. 2 shows a surgical tool comprising a periosteal elevator.In some embodiments of the present invention, flexible shaft 34 ishollow so as to allow the introduction of additional apparatus to theoperative site. FIG. 2 shows an embodiment in which a trocar 32 isintroduced through hollow flexible shaft 34.

Typically, endoscopic apparatus 30 is used to proceed with the surgicalprocedure subsequent to dissection of the contents of the greaterpalatine foramen, by inserting hollow sleeve 36 into the greaterpalatine foramen with the aid of handle 38. Once the hollow sleeve issuitably positioned, flexible shaft 34 with attached surgical tool 40and trocar 32 are typically inserted through hollow sleeve 36. In anembodiment, surgical tool 40 comprises a periosteal elevator. Trocar 32is typically advanced using a gentle 180 degree axial rotation, andsubperiosteal dissection is performed with the aide of surgical tool 40so as to detach the contents of the greater palatine canal from theosseous portion of the canal. Typically, the dissection is monitoredwith endoscopic visualization, while irrigation and suction are used asnecessary to maintain the site of dissection. Trocar 32 should typicallybe introduced about 2 centimeters relative to the bony entrance of thegreater palatine canal, with allowable variation for the anatomy ofindividual patients.

FIG. 3 illustrates shaft 34 and the anatomy of the pterygopalatine fossa50, which shows an SPG 52 adjacent to a sphenopalatine artery 54, inaccordance with an embodiment of the present invention. Thepterygopalatine fossa is a bilateral intraosseous space at thecraniofacial junction. Because of its location, it is consideredtogether with the structures of the paranasal sinuses. The fossaresembles a four-sided pyramid with an imaginary base, anterior,posterior and medial wall all converging at the vertex. The basecorresponds to the region of the orbital vertex. The anterior wall isbordered by a small vertical portion of the maxillary tuberosity closeto its junction with the palatine vertical plate. The medial wall isformed by the vertical plate of the palatine bone and is crossed by thesphenopalatine foramen. The posterior wall corresponds to the anteriorface of the pterygoid process of the sphenoid bone. The lateral walllies against the skull, sealed by fibrous tissue, and allows the passageof the vascular and nervous structures. The vertex of the pyramid is thejunction of the walls, where the palatine osseous canals connect thepterygopalatine fossa with the oral cavity through the hard palate.

A vidian nerve 57, contained in a vidian foramen 56, is seen to beconnected to SPG 52. Typically, the vidian foramen and nerve areapproached under direct endoscopic visualization, after the stepsdescribed hereinabove with reference to FIG. 2. Typically, hollowflexible shaft 34 (see also FIG. 2) is introduced towards vidian nerve57 and/or SPG 52.

FIG. 4A shows an electrode introducer 60, comprising a flexible rod 62,to which an electrode support 58 is attached, and a handle 64 formanipulating the introducer, in accordance with an embodiment of thepresent invention. Typically, electrode support 58 is introduced to theregion of the vidian nerve and the SPG via flexible shaft 34.

FIG. 4B shows flexible electrode support 58, rolled to fit inside shaft34, at a point in time as support 58 is advanced out from shaft 34, suchthat support 58 opens upon exiting the distal end of shaft 34, inaccordance with an embodiment of the present invention. Electrodes, suchas plate electrodes 66a, described hereinbelow with reference to FIG.5A, are affixed to one or more sites on the electrode support, and arepositioned to be in contact with a target site such as the SPG when thesupport unrolls.

FIGS. 5A, 5B, and 5C show several electrode configurations for use withelectrode support 58, in accordance with respective embodiments of thepresent invention. The three illustrated electrode configurations aretypically flat, providing a relatively large surface area for contactwith the SPG or other tissue. Additionally, the flexibility and flatthin shapes of the electrode support and the electrodes are conducive tobeing rolled up, for some applications, so as to fit through flexibleshaft 34 and subsequently return to essentially their initial flat shape(see FIG. 4B). FIG. 5A shows a simple plate electrode design comprisingtwo plate electrodes 66 a, which are each connected to respective leads65, typically but not necessarily by laser welding. Other embodimentscomprise more than two plate electrodes 66 a. Typically, plateelectrodes 66a comprise platinum/iridium or other suitable substancesknown in the art of tissue stimulation.

FIG. 5B shows an alternate electrode design where each of two compoundplate electrodes 66 b typically comprises a horizontal strip 67, towhich a plurality of vertical plates 69 is coupled. Typically, eachhorizontal strip 67 is coupled to a respective lead 65 by laser welding.Horizontal strip 67 and vertical plates 69 typically compriseplatinum/iridium or other suitable substances known in the art of tissuestimulation.

FIG. 5C shows another electrode design providing a large surface areafor contact with the SPG, comprising two shaped electrodes 66 c, whichare shaped to provide the desired electrical stimulation to the SPG. Inan embodiment, electrodes 66 c are formed by cutting the shapes out of asimple plate comprising platinum/iridium or other suitable substancesknown in the art of tissue stimulation.

For some applications, electrode support 58 shown in FIGS. 5A, 5B, and5C is about 4 mm by about 6-10 mm. The total contact surface areabetween the SPG (or other tissue) and the electrodes in the embodimentsshown in these figures is, for some applications, between about 0.5 mm²and about 2 mm².

FIG. 6 shows an electrode 68 that is configured to wrap around a nerve,in accordance with an embodiment of the present invention. Electrode 68is shown in the figure in a bipolar configuration, for placement atrespective longitudinal sites on the nerve. For some applications,electrode 68 comprises a single monopolar “hook” electrode. Typically,electrode 68 comprises two conductive strips 70, pre-bent to a curvedshape such that they can be placed during a procedure to wrap around atarget nerve, for example the vidian or ethmoidal nerves. The innerportion of conductive strips 70 is designated to be in contact with thetarget nerve (or only slightly separated therefrom), and provides theelectrical stimulation to the nerve. The outer surfaces of strips 70,i.e., those surfaces not in contact with the nerve, are typicallysheathed or otherwise coated in a non-conductive material 72, to reduceor eliminate stimulation of tissues surrounding the target nerve.

FIG. 7 shows details of flexible rod 62 (see FIGS. 4A and 4B), which isused in the placement of electrode support 58 and comprises one or moreelectrical leads 74 for transmitting electrical power to the electrodes(e.g., electrodes 66 a, 66 b, or 66 c) on electrode support 58, inaccordance with an embodiment of the present invention. Typically,electrical leads 74 are cast into a solid elastomer sheathing 76 toprovide a desired degree of flexibility and strength during theintroduction of the electrodes, and to also provide the isolation of theleads from bodily tissues and fluids.

FIG. 8 shows apparatus for supporting and protecting electrical leads 74while maintaining sufficient strength and flexibility, in accordancewith an embodiment of the present invention. Typically, leads 74 arethreaded through a hollow tube 80, chosen to provide appropriatestrength and flexibility, which typically comprises a plurality ofsupports 82 along the length of tube 80 for holding leads 74 andpreventing damage to the leads during introduction or operation of theelectrodes.

FIG. 9A shows a partially sectional view of a receiver 78, which isadapted to be coupled to the proximal end of rod 62 (FIG. 4A) by a base92 and to receive power and control signals from a control unit thatdrives electrodes, such as electrodes 66 a, 66 b, or 66 c, on electrodesupport 58, in accordance with an embodiment of the present invention.Receiver 78 comprises a coil 90 and an electronics pod 94, which arecoupled to a base 92 and adapted to receive power and drive theelectrodes. Typically, coil 90 is constructed using Drawn Filled Tubetechnology, and typically comprises a combination of MP35N and silver.In an embodiment, coil 90 is adapted to receive control and power inputswirelessly. By way of example but not limitation, RF electromagneticfields and/or oscillating magnetic fields are used to wirelessly powerand control the electrodes via coil 90 and electronics pod 94.

FIG. 9B shows a partially sectional view of a receiver 100, which isadapted to be coupled to the proximal end of rod 62 (FIG. 4A) by a base92 and to receive power and control signals from a control unit thatdrives electrodes, such as electrodes 66 a, 66 b, or 66 c, on electrodesupport 58, in accordance with an embodiment of the present invention.Receiver 100 comprises an electronics module 102, which comprises aplurality of connectors 104 for wired connections to a typicallynon-implanted control unit.

Typically, receivers 78 and 100 are coated with a non-permeable coatingsuch as, but not limited to, Parylene, which isolates the receiver fromphysiological fluids and tissues. Further typically, the receivers areencased in a relatively pliant layer such as an elastomer, which servesas an outer casing for the receiver.

Alternatively or additionally, techniques are used that are described inU.S. Provisional Patent Application 60/426,182, filed Nov. 14, 2002,entitled, “Stimulation circuitry and control of electronic medicaldevice,” which is assigned to the assignee of the present applicationand is incorporated herein by reference.

Typically, once electrode support 58 is properly placed, endoscopicdevice 30 (see FIG. 2) is removed from the patient, and receiver 78 orreceiver 100 remains in the patient, typically immediately above orbelow the hard palate or at the ridge of the eye, and is connected byleads to the electrodes on electrode support 58. Note that keyholeopening 42 in hollow sleeve 36 and slit 43 in handle 38 allow for theremoval of these items without affecting leads 74, because the leadspass through the keyhole and slit as the handle and sleeve are removed.Alternatively, sleeve 36 is made so as to split along its length priorto removal.

FIG. 10 shows the placement of electrode support 58 adjacent to SPG 52and the placement of a stimulator 112 comprising receiver 78 in thesupraperiosteal region of the hard palate of the patient, typically atmidline, in accordance with an embodiment of the present invention.Alternatively, stimulator 112 is implanted in the nasal cavity on theupper surface of the hard palate. Typically, stimulator 112 receivespower wirelessly from an external control unit temporarily placed in ornear the mouth. Stimulator 112 is typically fixed to the hard palatewith microscrews. Alternatively, the control unit powers and controlsstimulator 112 by a wired connection between the control unit and areceiver 100 (FIG. 9B) incorporated into the stimulator. Furtheralternatively, one or more lead wires are brought out through the skinand coupled to an external control unit.

Typically, but not necessarily, techniques described in PCT PatentPublication WO 01/85094 to Shalev and Gross, entitled, “Method andapparatus for stimulating the sphenopalatine ganglion to modifyproperties of the BBB and cerebral blood flow,” or the US national phaseapplication thereof, U.S. patent application Ser. No. 10/258,714, filedOct. 25, 2002, both of which are assigned to the assignee of the presentpatent application and incorporated herein by reference, are adapted foruse with the techniques of these embodiments of the present invention.In particular, electrodes implanted adjacent to the SPG, using therelatively minimally-invasive surgical techniques and associatedsurgical tools of the present invention, are driven by a stimulator(e.g. control unit), using control and driving circuitry and treatmentprotocols described therein, to control the blood brain barrier and/ortreat neurological symptoms or disease.

In an embodiment of the present invention, a combined trans-maxillarysinus and trans-nasal endoscopic-assisted approach to the SPG is used inorder to implant at least one electrode in a region of the SPG.Typically, to start the procedure, the patient is given a local andtopical anesthesia in the intraoral vestibulum at the area of the caninefossa, and a topical intranasal anesthesia at the region of the lateralnasal wall of the operated side. The posterior wall of the maxillarysinus is typically dissected, and the anterior part of thesphenopalatine fossa is dissected via a trans-maxillary approach.Typically, the dissection is performed approximately 0.5 mm from themedial wall of the maxillary sinus under direct endoscopicvisualization.

Typically, a complete nasal endoscopic examination is performed on bothsides and then under direct visualization an incision is made about0.4-about 0.8 mm under the second conchae on the operating side. Amucoperiosteal flap is typically raised posteriorly and inferiorlyfollowed by dissection and clamping of the sphenopalatine artery.Subsequently, under direct visualization, the lateral wall of the noseis typically penetrated and the sphenopalatine fossa is approached. Inan embodiment of the present invention, the surgeon now approaches theSPG via the trans-maxillary sinus. In another embodiment, the surgeonapproaches the SPG via the trans-nasal approach. The specific approachis typically dependent on the anatomical topography of the patient.

At this stage of the procedure, endoscopic device 30 (see FIG. 2) istypically inserted in the dissected tissue and used to place anelectrode adjacent to the SPG, as discussed hereinabove for theendoscopic transpalatine approach to the SPG.

Yet another embodiment of the present invention comprises an upperblepharoplasty approach to the anterior and/or posterior ethmoidalnerves, in order to implant at least one electrode adjacent to theanterior and/or posterior ethmoidal nerves. Typically, to start theprocedure, the patient's upper and lower eyelids are sterilized. A localanesthetic is typically applied to the upper eyelid. Once the anesthetichas taken effect, an incision in the skin following an eyelid crest istypically performed. In an embodiment, the incision is approximately 15mm long.

Once the skin has been dissected, the orbicularis muscle is typicallypassed through by performing a blunt dissection. Subsequently, a sharpincision of the periosteum, typically about 15 mm in length, is made onthe superomedial aspect of the orbit. Typically, the subperiostealtissue is then dissected to expose the anterior ethmoidal foramen andits contents, including the anterior ethmoidal nerve. Alternatively oradditionally, the dissection is performed so as to expose the posteriorethmoidal nerve. Once the anterior and/or posterior ethmoidal nerve hasbeen exposed, at least one electrode is implanted adjacent to the nerve.

FIG. 11 shows the placement of an electrode 120 adjacent to theposterior ethmoidal nerve 124 in the region of an orbital cavity 128, inaccordance with an embodiment of the present invention. Typically,electrode 120 is coupled to a stimulator 122 by a lead 130. Stimulator122 is typically fixed to the superior orbital rim. Following placementof electrode 120, lead 130, and stimulator 122, incisions in theperiosteum, muscle and skin are closed with standard surgicaltechniques.

Alternatively, electrode 120 is placed adjacent to an anterior ethmoidalnerve 126. Further alternatively, a plurality of electrodes 120 isplaced so as to stimulate both the anterior and the posterior ethmoidalnerves.

Typically, verification and/or optimization of the electrode nerveinterface after the electrodes are placed is performed by observing theeffects of stimulation on one or more physiological responses. Potentialobservations include, but are not limited to: (1) evaluating thevasodilatation of blood vessels of the eye, (2) assessment of cerebralblood flow by using trans-cranial Doppler, (3) assessment of foreheadperfusion by using Laser-Doppler, and (4) assessment of foreheadperfusion by a temperature sensor.

FIG. 12 is a schematic, pictorial illustration showing incisions 200 ina roof of oral cavity 20 and associated anatomical structures, wheredissection commences in a surgical procedure to access the SPG system,in accordance with an embodiment of the present invention. In thisembodiment, soft tissue is dissected to expose greater palatine foramen22 (see FIG. 1), in order to allow access via the greater palatine canalto the SPG system by means of a transpalatine approach.

Prior to beginning the surgical procedure, the patient is typicallyinstructed to rinse his mouth with an antimicrobial oral rinse, such as0.2% chlorhexidine solution, for at least about five minutes. For somepatients, the surgical procedure is performed under general anesthesiaTo begin the procedure, the patient is typically positioned with an openmouth (typically using a mouth gag). Greater palatine foramen 22(FIG. 1) is then located, typically by the anatomical landmark of secondupper molar 24. (Greater palatine foramen 22 is typically located 1 cmmedial to second upper molar 24 at the border between the hard and thesoft palates.) The area of greater palatine foramen 22 is anesthetized,such as by 2 ml lidocaine. A full-thickness about 3 cm mucogingivalincision 210 is made at the midline of the hard palate, including about0.5 cm of the soft palate. Two releasing incisions 212, about 1 cm each,are made at the ends of midline incision 210. Typically, electrosurgeryis used to make these releasing incisions in order to minimize bleeding.A mucoperiosteal flap 214 is raised, and the greater palatineneurovascular bundle is carefully exposed, typically using Jeter cleftpalate scissors and a periosteal elevator, such as an Obwegeserperiosteal elevator. The neuromuscular bundle is typically preservedusing a molt curette. Mucoperiosteal flap 214 is gently and firmlyretracted using a flap retractor, such as a Jensen flap retractor,revealing the contents of greater palatine foramen 22.

FIG. 13 is a schematic illustration of a stylet 240, which is the firstinstrument to be inserted into the greater palatine canal once thecontents of greater palatine foramen 22 have been dissected andrevealed, in accordance with an embodiment of the present invention.Stylet 240 comprises a handle 242 and a rod 244 coupled to the handle,such as with a screw (screw not shown). Rod 244 comprises a proximal rodshaft 246 and a narrower distal rod shaft 248. Proximal rod shaft 246typically has a length L₁ of between about 20 mm and about 150 mm, suchas about 88 mm or about 100 mm, and a diameter of between about 1.5 mmand about 6 mm, such as about 4 mm or about 4.6 mm. Distal rod shaft 248typically has a length L₂ of between about 3 mm and about 20 mm, such asabout 10 mm or about 12 mm, and a diameter of between about 1 mm andabout 1.5 mm, such as about 1.3 mm. A distal tip of distal rod shaft 248typically comprises a cutting implement 249, such as a blade. Typically,rod 244 is shaped so as to define a shoulder 250 between proximal rodshaft 246 and distal rod shaft 248. Shoulder 250 is adapted to preventinsertion of distal rod shaft 248 into the sphenopalatine fossa beyondthe depth of the greater palatine canal.

FIG. 14 is a schematic, pictorial illustration of a posterolateral roof280 of oral cavity 20 (FIG. 1), in accordance with an embodiment of thepresent invention. Shown in the figure are greater palatine foramen 22,a greater palatine canal 282, and a posterior wall 284 of greaterpalatine canal 282. During the surgical procedure, stylet 240 isinserted posteriorly through the greater palatine canal to the greaterpalatine neurovascular bundle, and supported against posterior wall 284.Stylet 240 is pushed vertically using a gentle plus and minus 45-degreeclockwise and counterclockwise rotational motion, until shoulder 250 ofstylet 240 (FIG. 13) reaches the exposed entrance to greater palatineforamen 22 (at the roof of the mouth).

FIGS. 15A and 15B are schematic illustrations of a passive tipperiosteal elevator 300 used to widen the path created using stylet 240,in accordance with embodiments of the present invention. Passive tipperiosteal elevator 300 comprises a handle 310 and a rod 312 coupled tothe handle, such as with a screw (screw not shown). Rod 312 comprises aproximal rod shaft 314 and a distal rod shaft 316, a distal tip 318 ofwhich is typically rounded. Proximal rod shaft 314 typically has alength L₃ of between about 30 mm and about 150 mm, such as about 70 mmor about 100 mm, and a diameter of between about 2 mm and about 6 mm,such as about 4 mm or about 4.6 mm. Distal rod shaft 316 typically has alength L₄ of between about 15 mm and about 50 mm, such as about 30 mm orabout 40 mm, and a diameter of between about 1 mm and about 2 mm.Typically, passive tip periosteal elevators having certain distal rodshaft 248 diameters (such as between about 1 mm and about 1.4 mm) have arounded distal rod shaft (configuration not shown in figures), whilepassive tip periosteal elevators having other distal rod shaft 248diameters (such as greater than about 1.4 mm) have a distal rod shaftwith at least one flattened surface 320, as shown in the figures.Optionally, flattened surface 320 is shaped to define file-like slots322, having a depth of about 0.2 mm, for example.

For some applications, distal rod shaft 316 is straight, as shown inFIG. 15A, while for other applications, distal rod shaft 316 is bent, asshown in FIG. 15B. Such a bend is typically located between about 3 mmand about 10 mm, such as about 4 mm, from distal tip 318, and typicallyhas an angle between about 5 degrees and about 15 degrees, such as about10 degrees.

During the surgical procedure, after stylet 240 has been removed, aseries of passive tip periosteal elevators 300, having successivelygreater distal rod shaft 316 diameters, is typically used to widen thepath created using stylet 240. First, the narrowest passive tipperiosteal elevator of the series (e.g., having a distal rod shaft 316diameter of about 1 mm) is introduced through the path created by stylet240, keeping tight contact between the instrument and posterior wall 284of greater palatine canal 282. This insertion is typically performedwith a plus and minus 45-degree clockwise and counterclockwiserotational motion and gentle abrading maneuver. If using a passive tipperiosteal elevator having a flattened surface, as describedhereinabove, the flattened surface is typically used for the abradingmaneuver. The passive tip periosteal elevator is typically inserted intothe greater palatine canal to a depth of about 25 mm. Alternatively, thedepth of the greater palatine canal is measured prior to or during theimplantation procedure, in which case the tip is inserted to themeasured depth. Typically, the depth of insertion is indicated on theelevator by one or more marks 324 on distal rod shaft 316.

The first, narrowest, passive tip periosteal elevator is removed, andthis widening step of the surgical procedure is repeated using elevatorshaving successively wider distal rod shaft diameters, until greaterpalatine canal 282 is widened, typically, to about 2 mm. Generally,irrigation and suction are performed between periosteal elevatorreplacements in order to remove osseous debris.

FIG. 16 is a schematic illustration of an implantable neural stimulator350, in accordance with an embodiment of the present invention.Stimulator 350 comprises an electrode support 352, a receiver 354, and aconnecting element 356, such as a connecting tube. (Other suitablestructures for connecting element 356 will be apparent to one ofordinary skill in the art, having read the disclosure of the presentpatent application.) Electrode support 352 comprises one or moreelectrodes 358, positioned on an electrode surface 360 of the support,such that the electrodes are in contact with a target site (e.g., theSPG) when stimulator 350 is implanted. For some applications, electrodes358 are arranged in the electrode configuration described hereinbelowwith reference to FIG. 17. Alternatively, for other applications,electrodes 358 are arranged in one of the electrode configurationsdescribed hereinabove with reference to FIGS. 5A, 5B, or 5C. Receiver354 receives power and control signals from a control unit that driveselectrodes 358. For some applications, receiver 354 is similar toreceiver 78 or receiver 100, described hereinabove with reference toFIG. 9A and FIG. 9B, respectively. Alternatively, other suitableconfigurations are utilized. Optionally, connecting element 356comprises one or more marks 362 that indicate the depth of insertion ofstimulator 350 into the greater palatine canal.

FIG. 17 shows an electrode configuration for use with electrode support352, in accordance with an embodiment of the present invention. In thisconfiguration, electrode support 352 comprises two insulated regions: aninsulated shaft region 370 and an insulated tip region 372. Electrodes358 comprise an annular electrode 374 and a rod electrode 376,electrically isolated from one another by insulated tip region 372.

FIG. 18 is a schematic illustration of an electrode introducer 400, inaccordance with an embodiment of the present invention. Introducer 400is used for introducing stimulator 350 into the greater palatine canal.Introducer 400 typically comprises a handle 402 for manipulating theintroducer, a rod 404, to which electrode support 352 (FIG. 16) isattached, and a protective sleeve 406.

FIG. 19 is a schematic illustration (not necessarily to scale) ofstimulator 350 mounted on electrode introducer 400, in accordance withan embodiment of the present invention. Stimulator 350 is mounted onelectrode introducer 400 by inserting electrode support 352 intoprotective sleeve 406.

During the surgical procedure, after greater palatine canal 282 has beenwidened, electrode introducer 400 is inserted into greater palatinecanal 282, typically to depth of about 25 mm. Alternatively, the depthof the greater palatine canal is measured prior to or during theimplantation procedure, in which case the introducer is inserted to themeasured depth. If connecting element 356 comprises marks 362, asdescribed hereinabove with reference to FIG. 16, such marks aretypically used to determine the depth of the introducer. Typically,electrode surface 360 of stimulator 350 is placed in contact with theposterior aspect of the SPG. Mucoperiosteal flap 214 (FIG. 12) issutured over receiver 354, which is located flush with the palatinebone, typically using forceps, such as Adson forceps, and a needleholder.

FIG. 20 shows the placement of electrode support 352 posteriorlyadjacent to SPG 52 and the placement of a stimulator 380 comprisingreceiver 354 in the supraperiosteal region of the hard palate of thepatient, typically at midline, in accordance with an embodiment of thepresent invention. Alternatively, stimulator 112 is implanted in thenasal cavity on the upper surface of the hard palate. Typically,stimulator 380 receives power wirelessly from an external control unittemporarily placed in or near the mouth. Stimulator 380 is typicallyfixed to the hard palate with microscrews. Further alternatively, one ormore lead wires are brought out through the skin and coupled to anexternal control unit. Still further alternatively, stimulator 380 isbattery powered, and comprises control circuitry to allow it to operateindependently of outside control.

In some embodiments, techniques described herein are practiced incombination with techniques described in one or both of the followingco-assigned US applications: (i) U.S. patent application Ser. No.10/294,310, filed Nov. 14, 2002, and a corresponding PCT applicationclaiming priority therefrom, filed on even date herewith, entitled,“Stimulation for treating eye pathologies,” and (ii) U.S. ProvisionalPatent Application 60/426,182, filed Nov. 14, 2002, entitled,“Stimulation circuitry and control of electronic medical device.” All ofthese applications are incorporated herein by reference.

Techniques described in this application may be practiced in combinationwith methods and apparatus described in one or more of the followingpatent applications, which are assigned to the assignee of the presentpatent application and are incorporated herein by reference:

-   -   U.S. patent application Ser. No. 10/258,714, filed Oct. 25,        2002, entitled, “Method and apparatus for stimulating the        sphenopalatine ganglion to modify properties of the BBB and        cerebral blood flow,” or the above-referenced PCT Publication WO        01/85094    -   U.S. Provisional Patent Application 60/364,451, filed Mar. 15,        2002, entitled, “Applications of stimulating the sphenopalatine        ganglion (SPG)”    -   U.S. Provisional Patent Application 60/368,657, filed Mar. 28,        2002, entitled, “SPG Stimulation”    -   U.S. Provisional Patent Application 60/376,048, filed Apr. 25,        2002, entitled, “Methods and apparatus for modifying properties        of the BBB and cerebral circulation by using the neuroexcitatory        and/or neuroinhibitory effects of odorants on nerves in the        head”    -   U.S. Provisional Patent Application 60/388,931, filed Jun. 14,        2002, entitled “Methods and systems for management of        Alzheimer's disease”    -   U.S. Provisional Patent Application 60/400,167, filed Jul. 31,        2002, entitled, “Delivering compounds to the brain by modifying        properties of the BBB and cerebral circulation”    -   U.S. Provisional Patent Application 60/426,180, filed Nov. 14,        2002, entitled, “Surgical tools and techniques for        sphenopalatine ganglion stimulation”    -   U.S. Provisional Patent Application 60/426,182, filed Nov. 14,        2002, entitled, “Stimulation circuitry and control of electronic        medical device”    -   U.S. patent application Ser. No. 10/294,310, filed Nov. 14,        2002, entitled, “SPG stimulation for treating eye pathologies”    -   U.S. patent application Ser. No. 10/294,343, filed Nov. 14,        2002, and a corresponding PCT application claiming priority        therefrom, filed on even date herewith, entitled,        “Administration of anti-inflammatory drugs into the CNS”    -   U.S. Provisional Patent Application 60/426,181, filed Nov. 14,        2002, entitled, “Stimulation for treating ear pathologies”    -   U.S. Provisional Patent Application 60/448,807, filed Feb. 20,        2003, entitled, “Stimulation for treating autoimmune-related        disorders of the CNS”    -   U.S. Provisional Patent Application 60/461,232 to Gross et al.,        filed Apr. 8, 2003, entitled, “Treating abnormal conditions of        the mind and body by modifying properties of the blood-brain        barrier and cephalic blood flow”    -   a PCT Patent Application to Shalev, filed Apr. 25, 2003,        entitled, “Methods and apparatus for modifying properties of the        BBB and cerebral circulation by using the neuroexcitatory and/or        neuroinhibitory effects of odorants on nerves in the head”    -   a U.S. provisional patent application, filed Sep. 26, 2003,        entitled, “Diagnostic applications of stimulation”    -   a U.S. patent application, filed Oct. 2, 2003, entitled,        “Targeted release of nitric oxide in the brain circulation for        opening the BBB”    -   a PCT patent application, filed on even date herewith,.        entitled, “Stimulation circuitry and control of electronic        medical device”    -   a PCT patent application, filed on even date herewith, entitled,        “Stimulation for treating ear pathologies”

It is noted that the figures depicting embodiments of the presentinvention are not necessarily drawn to scale, and, instead, may changecertain dimensions in order to more clearly demonstrate some aspects ofthe invention.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1. A method comprising: widening at least a portion of a greaterpalatine canal of a subject; passing a treatment stimulation devicethrough a greater palatine foramen of the subject; bringing the deviceinto contact with a vicinity of a site of the subject, the site selectedfrom the group consisting of: a sphenopalatine ganglion (SPG) of thesubject and a neural tract originating in or leading to the SPG;applying stimulation with the device; and configuring the stimulation tobe sufficient to induce a change in cerebral blood flow of the subject.2. The method according to claim 1, wherein the site includes the SPG ofthe subject, and wherein bringing the device into contact with thevicinity of the site comprises bringing the device into contact with thevicinity of the SPG.
 3. The method according to claim 1, wherein thesite includes a vidian nerve of the subject, and wherein bringing thedevice into contact with the vicinity of the site comprises bringing thedevice into contact with the vicinity of the vidian nerve.
 4. The methodaccording to claim 1, wherein the site includes an ethmoidal nerve ofthe subject, and wherein bringing the device into contact with thevicinity of the site comprises bringing the device into contact with thevicinity of the ethmoidal nerve.
 5. The method according to claim 1,wherein the site includes a retro-orbital branch of the SPG of thesubject, and wherein bringing the device into contact with the vicinityof the site comprises bringing the device into contact with theretro-orbital branch.
 6. The method according to claim 1, whereinbringing the device into contact comprises: observing one or morephysiological responses of the subject to the stimulation; and verifyingdesired placement of the device responsive to the observation.
 7. Themethod according to claim 1, wherein the stimulation device includes atleast one electrode, and wherein bringing the device into contactcomprises bringing the electrode into contact with the vicinity of thesite.
 8. The method according to claim 7, wherein bringing the electrodeinto contact comprises wrapping the electrode around a nerve of thesubject in the vicinity of the site.
 9. The method according to claim 1,wherein the stimulation device includes a stimulator, the methodcomprising fixing the stimulator to a hard palate of the subject. 10.The method according to claim 9, wherein fixing the stimulator to thehard palate comprises coupling the stimulator to a supraperiostealregion of the hard palate.
 11. The method according to claim 9, whereinfixing the stimulator to the hard palate comprises coupling thestimulator to an upper surface of the hard palate in a nasal cavity ofthe subject.
 12. The method according to claim 9, wherein fixing thestimulator to the hard palate comprises coupling the stimulator to alower surface of the hard palate.
 13. The method according to claim 1,wherein passing the device through the greater palatine foramencomprises determining a depth of insertion of the device in a greaterpalatine canal of the subject by observing at least one mark on thedevice indicative of the depth of the insertion.
 14. The methodaccording to claim 1, wherein widening the greater palatine canal of thesubject comprises using a series of tools having successively greaterdiameters.
 15. The method according to claim 1, wherein passing thedevice through the greater palatine foramen comprises mounting thedevice on an introducer, and passing the introducer through the greaterpalatine foramen.
 16. The method according to claim 1, wherein bringingthe device into contact comprises implanting the device in the vicinityof the site.
 17. The method according to claim 1, wherein widening thegreater palatine canal comprises using a series of periosteal elevatorshaving successively greater diameters.
 18. The method according to claim1, wherein widening the greater palatine canal comprises abrading. 19.The method according to claim 1, wherein widening the greater palatinecanal comprises removing osseous debris.
 20. A method comprising:widening at least a portion of a greater palatine canal of a subject;passing a treatment stimulation device through the at least a portion ofthe greater palatine canal; bringing the device into contact with avicinity of a site of the subject, the site selected from the groupconsisting of: a sphenopalatine ganglion (SPG) of the subject and aneural tract originating in or leading to the SPG; and applyingstimulation with the device; and configuring the stimulation to besufficient to induce a change in cerebral blood flow of the subject. 21.The method according to claim 20, wherein passing the device through theportion of the greater palatine canal comprises determining a depth ofinsertion of the device in the greater palatine canal by observing atleast one mark on the device indicative of the depth of the insertion.22. The method according to claim 20, wherein passing the device throughthe at least a portion of the greater palatine canal comprises passingthe device through at least about 2 cm of the greater palatine canal.23. The method according to claim 20, wherein widening the portioncomprises using a series of tools having successively greater diameters.24. The method according to claim 20, wherein passing the device throughthe at least a portion of the greater palatine canal comprises mountingthe device on an introducer, and passing the introducer through theportion.
 25. The method according to claim 20, wherein bringing thedevice into contact comprises implanting the device in the vicinity ofthe site.
 26. The method according to claim 20, wherein the siteincludes the SPG of the subject, and wherein bringing the device intocontact with the vicinity of the site comprises bringing the device intocontact with the vicinity of the SPG.
 27. The method according to claim20, wherein the site includes a vidian nerve of the subject, and whereinbringing the device into contact with the vicinity of the site comprisesbringing the device into contact with the vicinity of the vidian nerve.28. The method according to claim 20, wherein the site includes anethmoidal nerve of the subject, and wherein bringing the device intocontact with the vicinity of the site comprises bringing the device intocontact with the vicinity of the ethmoidal nerve.
 29. The methodaccording to claim 20, wherein the site includes a retro-orbital branchof the SPG of the subject, and wherein bringing the device into contactwith the vicinity of the site comprises bringing the device into contactwith the retro-orbital branch.
 30. The method according to claim 20,wherein bringing the device into contact comprises: observing one ormore physiological responses of the subject to the stimulation; andverifying desired placement of the device responsive to the observation.31. The method according to claim 20, wherein the stimulation deviceincludes at least one electrode, and wherein bringing the device intocontact comprises bringing the electrode into contact with the vicinityof the site.
 32. The method according to claim 31, wherein bringing theelectrode into contact comprises wrapping the electrode around a nerveof the subject in the vicinity of the site.
 33. The method according toclaim 20, wherein the stimulation device includes a stimulator, themethod comprising fixing the stimulator to a hard palate of the subject.34. The method according to claim 33, wherein fixing the stimulator tothe hard palate comprises coupling the stimulator to a supraperiostealregion of the hard palate.
 35. The method according to claim 33, whereinfixing the stimulator to the hard palate comprises coupling thestimulator to an upper surface of the hard palate in a nasal cavity ofthe subject.
 36. The method according to claim 33, wherein fixing thestimulator to the hard palate comprises coupling the stimulator to alower surface of the hard palate.
 37. The method according to claim 20,wherein widening the portion comprises using a series of periostealelevators having successively greater diameters.
 38. The methodaccording to claim 20, wherein widening the portion comprises abrading.39. The method according to claim 20, wherein widening the portioncomprises removing osseous debris.
 40. A method comprising: passing atreatment stimulation device through a greater palatine foramen of asubject; bringing the device into contact with a vicinity of a site ofthe subject, the site selected from the group consisting of: asphenopalatine ganglion (SPG) of the subject and a neural tractoriginating in or leading to the SPG; applying stimulation with thedevice; and configuring the stimulation to be sufficient to modulatepermeability of a blood-brain-barrier of the subject.
 41. The methodaccording to claim 40, wherein the site includes the SPG of the subject,and wherein bringing the device into contact with the vicinity of thesite comprises bringing the device into contact with the vicinity of theSPG.
 42. The method according to claim 40, wherein the site includes avidian nerve of the subject, and wherein bringing the device intocontact with the vicinity of the site comprises bringing the device intocontact with the vicinity of the vidian nerve.
 43. The method accordingto claim 40, wherein the site includes an ethmoidal nerve of thesubject, and wherein bringing the device into contact with the vicinityof the site comprises bringing the device into contact with the vicinityof the ethmoidal nerve.
 44. The method according to claim 40, whereinthe site includes a retro-orbital branch of the SPG of the subject, andwherein bringing the device into contact with the vicinity of the sitecomprises bringing the device into contact with the retro-orbitalbranch.
 45. The method according to claim 40, wherein bringing thedevice into contact comprises: observing one or more physiologicalresponses of the subject to the stimulation; and verifying desiredplacement of the device responsive to the observation.
 46. The methodaccording to claim 40, wherein the stimulation device includes astimulator, the method comprising fixing the stimulator to a hard palateof the subject.
 47. The method according to claim 46, wherein fixing thestimulator to the hard palate comprises coupling the stimulator to asupraperiosteal region of the hard palate.
 48. The method according toclaim 46, wherein fixing the stimulator to the hard palate comprisescoupling the stimulator to an upper surface of the hard palate in anasal cavity of the subject.
 49. The method according to claim 46,wherein fixing the stimulator to the hard palate comprises coupling thestimulator to a lower surface of the hard palate.
 50. The methodaccording to claim 40, wherein bringing the device into contactcomprises implanting the device in the vicinity of the site.
 51. Themethod according to claim 40, wherein passing the device through thegreater palatine foramen comprises widening a greater palatine canal ofthe subject.
 52. The method according to claim 51, wherein widening thegreater palatine canal comprises abrading.
 53. The method according toclaim 51, wherein widening the greater palatine canal comprises removingosseous debris.
 54. A method comprising: passing a treatment stimulationdevice through at least a portion of a greater palatine canal of asubject; bringing the device into contact with a vicinity of a site ofthe subject, the site selected from the group consisting of: asphenopalatine ganglion (SPG) of the subject and a neural tractoriginating in or leading to the SPG; applying stimulation with thedevice; and configuring the stimulation to be sufficient to modulatepermeability of a blood-brain-barrier of the subject.
 55. The methodaccording to claim 54, wherein bringing the device into contactcomprises implanting the device in the vicinity of the site.
 56. Themethod according to claim 54, wherein the site includes the SPG of thesubject, and wherein bringing the device into contact with the vicinityof the site comprises bringing the device into contact with the vicinityof the SPG.
 57. The method according to claim 54, wherein the siteincludes a vidian nerve of the subject, and wherein bringing the deviceinto contact with the vicinity of the site comprises bringing the deviceinto contact with the vicinity of the vidian nerve.
 58. The methodaccording to claim 54, wherein the site includes an ethmoidal nerve ofthe subject, and wherein bringing the device into contact with thevicinity of the site comprises bringing the device into contact with thevicinity of the ethmoidal nerve.
 59. The method according to claim 54,wherein the site includes a retro-orbital branch of the SPG of thesubject, and wherein bringing the device into contact with the vicinityof the site comprises bringing the device into contact with theretro-orbital branch.
 60. The method according to claim 54, whereinbringing the device into contact comprises: observing one or morephysiological responses of the subject to the stimulation; and verifyingdesired placement of the device responsive to the observation.
 61. Themethod according to claim 54, wherein the stimulation device includes astimulator, the method comprising fixing the stimulator to a hard palateof the subject.
 62. The method according to claim 61, wherein fixing thestimulator to the hard palate comprises coupling the stimulator to asupraperiosteal region of the hard palate.
 63. The method according toclaim 61, wherein fixing the stimulator to the hard palate comprisescoupling the stimulator to an upper surface of the hard palate in anasal cavity of the subject.
 64. The method according to claim 61,wherein fixing the stimulator to the hard palate comprises coupling thestimulator to a lower surface of the hard palate.
 65. The methodaccording to claim 54, wherein passing the device through the at least aportion of the greater palatine canal comprises widening the portion.66. The method according to claim 65, wherein widening the portionpalatine canal comprises abrading.
 67. The method according to claim 65,wherein widening the portion comprises removing osseous debris.